Aquaporin 4 antibody (AQP4-Ab)–negative patients with longitudinally extensive transverse myelitis (LETM) behave differently from those with AQP4-Ab. Aquaporin 4 antibody–negative neuromyelitis optica (NMO) is rare when good assays are used.
To assess if AQP4-Ab–negative patients with LETM share similar disease characteristics with AQP4-Ab–positive patients or whether they have distinct features and alternative diagnoses.
We collated clinical and paraclinical data on patients with LETM identified through the Oxford NMO clinical database. Aquaporin 4 antibodies were tested using 2 sensitive assays. We describe the features of patients with LETM, compare findings between patients with and without AQP4-Ab, and describe alternative diagnoses in AQP4-Ab–negative patients.
Single specialist UK center for NMO.
Seventy-six adult patients with LETM.
Main Outcomes and Measures
Comparison of clinical and paraclinical data.
Fifty-eight percent of patients were AQP4-Ab positive. Alternative diagnoses could usually be identified in AQP4-Ab–negative patients, including those fulfilling NMO diagnostic criteria. Only 6.5% of patients had “true” seronegative NMO and 6.5% had idiopathic LETM. There were some important differences between AQP4-Ab–positive and –negative cases, including older onset age, higher proportion of females, lower incidence of simultaneous optic neuritis, lower frequency of conus involvement, and higher prevalence of coexisting autoimmune disorders in AQP4-Ab–positive cases. Attack severity and degree of recovery were similar in the 2 groups.
Conclusions and Relevance
Patients with LETM without AQP4-Ab include a number of different diagnostic categories and it is not surprising therefore that they show important differences compared with AQP4-Ab–positive patients, even when considering only those fulfilling current NMO diagnostic criteria. Thus, we suggest that diagnoses such as myelin-oligodendrocyte glycoprotein antibody disease, multiple sclerosis, acute disseminated encephalomyelitis, and postinfectious disorders should be exclusions in the NMO diagnostic criteria and AQP4-Ab–positive and antibody–negative NMO/NMO spectrum disorder cohorts should be analyzed separately.